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First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up.

Abstract OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data. METHODS Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve. The mechanism of injury included a boat propeller and a gunshot wound. The SCs were obtained from both the sural nerve and damaged sciatic nerve stump. The SCs were expanded and purified in culture by using heregulin β1 and forskolin. Repair was performed with sural nerve grafts, SCs in suspension, and a Duragen graft to house the construct. Follow-up was 36 and 12 months for the patients in Cases 1 and 2, respectively. RESULTS The patient in Case 1 had a boat propeller injury with complete transection of both sciatic divisions at midthigh. The graft length was approximately 7.5 cm. In the postoperative period the patient regained motor function (Medical Research Council [MRC] Grade 5/5) in the tibial distribution, with partial function in peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory function was also achieved, and neuropathic pain was completely resolved. The patient in Case 2 sustained a gunshot wound to the leg, with partial disruption of the tibial division of the sciatic nerve at the midthigh. The graft length was 5 cm. Postoperatively the patient regained complete motor function of the tibial nerve, with partial return of sensation. Long-term follow-up with both MRI and ultrasound demonstrated nerve graft continuity and the absence of tumor formation at the repair site. CONCLUSIONS Presented here are the first 2 cases in which autologous SCs were used to supplement human peripheral nerve repair in long-segment injury. Both patients had significant improvement in both motor and sensory function with correlative imaging. This study demonstrates preliminary safety and efficacy of SC transplantation for peripheral nerve repair.
PMID
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The Use of Autologous Schwann Cells to Supplement Sciatic Nerve Repair With a Large Gap: First in Human Experience.

Authors

Mayor MeshTerms
Keywords

AGC = axon guidance channel

DN4 = Neuropathic Pain Diagnostic Questionnaire

ISO = International Organization for Standardization

MRC = Medical Research Council

SC = Schwann cell

Schwann cells

nerve injury

repair

sciatic nerve

sural nerve

transplantation

Journal Title neurosurgical focus
Publication Year Start




PMID- 28245668
OWN - NLM
STAT- MEDLINE
DA  - 20170301
DCOM- 20170308
LR  - 20170308
IS  - 1092-0684 (Electronic)
IS  - 1092-0684 (Linking)
VI  - 42
IP  - 3
DP  - 2017 Mar
TI  - First human experience with autologous Schwann cells to supplement sciatic nerve 
      repair: report of 2 cases with long-term follow-up.
PG  - E2
LID - 10.3171/2016.12.FOCUS16474 [doi]
AB  - OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to
      surgeons because insufficient donor tissue limits repair. Multiple supplemental
      approaches have been investigated, including the use of Schwann cells (SCs). The 
      authors present the first 2 cases using autologous SCs to supplement a peripheral
      nerve graft repair in humans with long-term follow-up data. METHODS Two patients 
      were enrolled in an FDA-approved trial to assess the safety of using expanded
      populations of autologous SCs to supplement the repair of long-segment injuries
      to the sciatic nerve. The mechanism of injury included a boat propeller and a
      gunshot wound. The SCs were obtained from both the sural nerve and damaged
      sciatic nerve stump. The SCs were expanded and purified in culture by using
      heregulin beta1 and forskolin. Repair was performed with sural nerve grafts, SCs 
      in suspension, and a Duragen graft to house the construct. Follow-up was 36 and
      12 months for the patients in Cases 1 and 2, respectively. RESULTS The patient in
      Case 1 had a boat propeller injury with complete transection of both sciatic
      divisions at midthigh. The graft length was approximately 7.5 cm. In the
      postoperative period the patient regained motor function (Medical Research
      Council [MRC] Grade 5/5) in the tibial distribution, with partial function in
      peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory 
      function was also achieved, and neuropathic pain was completely resolved. The
      patient in Case 2 sustained a gunshot wound to the leg, with partial disruption
      of the tibial division of the sciatic nerve at the midthigh. The graft length was
      5 cm. Postoperatively the patient regained complete motor function of the tibial 
      nerve, with partial return of sensation. Long-term follow-up with both MRI and
      ultrasound demonstrated nerve graft continuity and the absence of tumor formation
      at the repair site. CONCLUSIONS Presented here are the first 2 cases in which
      autologous SCs were used to supplement human peripheral nerve repair in
      long-segment injury. Both patients had significant improvement in both motor and 
      sensory function with correlative imaging. This study demonstrates preliminary
      safety and efficacy of SC transplantation for peripheral nerve repair.
FAU - Gersey, Zachary C
AU  - Gersey ZC
AD  - Department of Neurological Surgery and the Miami Project to Cure Paralysis,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Burks, S Shelby
AU  - Burks SS
AD  - Department of Neurological Surgery and the Miami Project to Cure Paralysis,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Anderson, Kim D
AU  - Anderson KD
AD  - Department of Neurological Surgery and the Miami Project to Cure Paralysis,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Dididze, Marine
AU  - Dididze M
AD  - Department of Neurological Surgery and the Miami Project to Cure Paralysis,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Khan, Aisha
AU  - Khan A
AD  - Department of Neurological Surgery and the Miami Project to Cure Paralysis,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Dietrich, W Dalton
AU  - Dietrich WD
AD  - Department of Neurological Surgery and the Miami Project to Cure Paralysis,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Levi, Allan D
AU  - Levi AD
AD  - Department of Neurological Surgery and the Miami Project to Cure Paralysis,
      University of Miami Miller School of Medicine, Miami, Florida.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Neurosurg Focus
JT  - Neurosurgical focus
JID - 100896471
SB  - IM
MH  - Accidents
MH  - Adult
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Schwann Cells/physiology/*transplantation
MH  - Sciatic Nerve/*injuries/*surgery
MH  - Sciatic Neuropathy/diagnostic imaging/*surgery
MH  - Sural Nerve/physiology/*transplantation
MH  - Transplantation, Autologous
MH  - Wounds, Gunshot/diagnostic imaging/*surgery
OTO - NOTNLM
OT  - *AGC = axon guidance channel
OT  - *DN4 = Neuropathic Pain Diagnostic Questionnaire
OT  - *ISO = International Organization for Standardization
OT  - *MRC = Medical Research Council
OT  - *SC = Schwann cell
OT  - *Schwann cells
OT  - *nerve injury
OT  - *repair
OT  - *sciatic nerve
OT  - *sural nerve
OT  - *transplantation
EDAT- 2017/03/02 06:00
MHDA- 2017/03/09 06:00
CRDT- 2017/03/02 06:00
AID - 10.3171/2016.12.FOCUS16474 [doi]
PST - ppublish
SO  - Neurosurg Focus. 2017 Mar;42(3):E2. doi: 10.3171/2016.12.FOCUS16474.

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